The study will evaluate risk factors for amyotrophic lateral sclerosis (ALS) and delineate the clinical course of patients with ALS. Exposure to a neurotoxin and effects of physical activity are the factors of greatest interest. Clues about a possible toxin will be sought by obtaining a history of exposures through work, hobbies and diet. A quantitative history of physical activity on the job, in the home and during leisure time will be obtained in hopes of clarifying the mechanism by which vigorous activities influence the risk of disease. Questions about physical activity include: intensity, estimated by caloric expenditure; setting, such as work place, indoor sport or outdoor sport; type, such as endurance versus power exercise; and the temporal relation of physical activity and disease onset. Other factors raised in previous epidemiologic studies will be considered, including medication use, history of trauma and fractures, history of electrical shock, family history of ALS and history of travel to the western Pacific region. Risk factors will be evaluated using a population-based, case-control study. Between 1 July 1990 and 30 June 1994, all residents of three western Washington counties (King, Pierce and Snohomish) who are diagnosed by a neurologist as having ALS will be identified, enrolled in the study, and followed until 30 June 1995. Based on the reported incidence of ALS and death certificate data from these three counties, we conservatively estimate enrolling 120 cases over four years. For each case, two controls will be identified using random digit telephone dialing. Controls will be matched to cases for age and gender. Information about exposure to the risk factors of interest will be obtained by personal interview of the cases and controls. Descriptive information about the clinical course of patients with ALS will come from a minimum one-year to a maximum five-year follow-up of these patients. This will include regular telephone follow-up, review of the patients' medical records, and review of death certificates and autopsy reports, when appropriate. Analysis of the case-control study will include estimates of relative risks using both univariate and multivariable techniques. Descriptive statistics and survival analyses will be used to summarize the clinical course and prognosis of this incident cohort of patients with ALS. The long-term goal of this study is to reduce the occurrence of this devastating disease by better understanding its causes.